Testing Sunitinib As Potentially Targeted Treatment In Cancers With CKIT Genetic Changes (MATCH - Subprotocol V)

Study Overview

Testing Sunitinib as Potentially Targeted Treatment in Cancers With cKIT Genetic Changes (MATCH - Subprotocol V)

This phase II MATCH treatment trial tests how well sunitinib in treating patients with cancer that has certain genetic changes. Sunitinib is in a class of medications called kinase inhibitors. It is used in patients whose cancer has a certain mutation (change) in the cKIT gene. It works by blocking the action of mutated cKIT that signals cancer cells to multiply. This helps to stop or slow the spread of cancer cells.

PRIMARY OBJECTIVE: I. To evaluate the proportion of patients with objective response (OR) to targeted study agent(s) in patients with advanced refractory cancers/lymphomas/multiple myeloma. SECONDARY OBJECTIVES: I. To evaluate the proportion of patients alive and progression free at 6 months of treatment with targeted study agent in patients with advanced refractory cancers/lymphomas/multiple myeloma. II. To evaluate time until death or disease progression. III. To identify potential predictive biomarkers beyond the genomic alteration by which treatment is assigned or resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and imaging-based assessment platforms. IV. To assess whether radiomic phenotypes obtained from pre-treatment imaging and changes from pre- through post-therapy imaging can predict objective response and progression free survival and to evaluate the association between pre-treatment radiomic phenotypes and targeted gene mutation patterns of tumor biopsy specimens. OUTLINE: Patients receive sunitinib orally (PO) once daily (QD) on days 1-28 of each cycle. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo computed tomography (CT) or magnetic resonance imaging (MRI) during screening and on study, as well as during follow-up as clinically necessary. Patients also undergo echocardiography (ECHO) or nuclear study throughout the trial as clinically necessary. Patients undergo biopsies and blood sample collection on study. After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 1 year. THE MATCH SCREENING TRIAL: Please see NCT02465060 for information on the MATCH Screening Protocol and applicable documents.

Advanced Lymphoma
Advanced Malignant Solid Neoplasm
Refractory Lymphoma
Refractory Malignant Solid Neoplasm
Refractory Multiple Myeloma

PROCEDURE: Biopsy
PROCEDURE: Biospecimen Collection
PROCEDURE: Computed Tomography
PROCEDURE: Echocardiography
PROCEDURE: Magnetic Resonance Imaging
PROCEDURE: Radionuclide Imaging
DRUG: Sunitinib

NCI-2024-01135
NCI-2024-01135 (REGISTRY Identifier) (REGISTRY: CTRP (Clinical Trial Reporting Program))
EAY131-V (OTHER Identifier) (OTHER: ECOG-ACRIN Cancer Research Group)
EAY131-V (OTHER Identifier) (OTHER: CTEP)
U10CA180820 (U.S. NIH Grant/Contract)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2024-04-27	Results First Submitted 2025-02-13	Last Update Submitted that met QC Criteria 2025-03-04
First Submitted that Met QC Criteria 2024-04-27	Results First Submitted that Met QC Criteria 2025-03-04	Last Update Posted (ACTUAL) 2025-03-25
First Posted (ACTUAL) 2024-04-30	Results First Posted 2025-03-25	Last Verified 2025-03

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Treatment (sunitinib) Patients receive sunitinib 50 mg PO QD on days 1-28 of each cycle. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT or MRI during screening and on study, as well as during follow	PROCEDURE: Biopsy Undergo biopsy PROCEDURE: Biospecimen Collection Undergo blood sample collection PROCEDURE: Computed Tomography Undergo CT scan PROCEDURE: Echocardiography Undergo ECHO PROCEDURE: Magnetic Resonance Imaging Undergo MRI PROCEDURE: Radionuclide Imaging Undergo nuclear study DRUG: Sunitinib Given PO

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Treatment (sunitinib)

Patients receive sunitinib 50 mg PO QD on days 1-28 of each cycle. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT or MRI during screening and on study, as well as during follow

PROCEDURE: Biopsy

Undergo biopsy

PROCEDURE: Biospecimen Collection

Undergo blood sample collection

PROCEDURE: Computed Tomography

Undergo CT scan

PROCEDURE: Echocardiography

Undergo ECHO

PROCEDURE: Magnetic Resonance Imaging

Undergo MRI

PROCEDURE: Radionuclide Imaging

Undergo nuclear study

DRUG: Sunitinib

Given PO

Primary Outcome Measures	Measure Description	Time Frame
Objective Response Rate (ORR)	ORR is defined as the percentage of patients whose tumors have a complete or partial response to treatment among analyzable patients. Objective response is defined consistent with Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. Details about how to define complete response and partial response can be found in the master protocol. 90% two-sided binomial exact confidence interval is calculated for ORR.* For treatments given in 21 day (3 week) cycles: every 3 cycles (9 weeks) for the first 33 cycles, and every 4 cycles thereafter (12 weeks) * For treatments given in 28 day (4 week) cycles: every 2 cycles (8 weeks) for the first 26 cycles, and every three cycles thereafter (12 weeks) * For treatments given in 42 day (6 week) cycles: every 2 cycles (12 weeks)	Tumor assessments occurred at baseline, then every 3 months if patient is < 2 years from study entry, and every 6 months thereafter until disease progression, up to 3 years post registration

Secondary Outcome Measures	Measure Description	Time Frame
6-month Progression Free Survival (PFS)	Progression free survival is defined as time from treatment start date to date of progression or death from any cause, whichever occurs first. Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. Please refer to the protocol for detailed definitions of disease progression. 6 month PFS rate was estimated using the Kaplan-Meier method, which can provide a point estimate for any specific time point.	Tumor assessments occurred at baseline, then every 3 months if patient is < 2 years from study entry, and every 6 months thereafter until disease progression, up to 3 years post registration
Progression Free Survival	PFS was defined as time from treatment start date to date of disease progression or death from any causes, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method. Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. Please refer to the protocol for detailed definitions of disease progression.	Tumor assessments occurred at baseline, then every 3 months if patient is < 2 years from study entry, and every 6 months thereafter until disease progression, up to 3 years post registration

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Patients must have met applicable eligibility criteria in the Master MATCH Protocol EAY131/ NCI-2015-00054 prior to registration to treatment subprotocol
Patients must fulfill all eligibility criteria of MATCH Master Protocol at the time of registration to treatment step (Step 1, 3, 5, 7)
Patients must have a somatic cKIT mutation in exon 9, 11, 13 or 14, excluding exon 17 or 18 mutations, activating PDGFRA or PDGFRB variants and fusions, or another aberration, as identified via the MATCH Master Protocol

Actionable mutations of interest (aMOIs)for information on the inclusion and exclusion mutations, along with the corresponding levels of evidence (LOE)
Total bilirubin must be within normal institutional limits
Creatinine must be within normal institutional limits. OR Creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
Serum calcium must be =< 12.0 mg/dL
Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have no clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block)
Patients with known left ventricular dysfunction must have ECHO or a nuclear study (multigated acquisition scan [MUGA] or first pass) within 4 weeks prior to registration to treatment and must not have left ventricular ejection fraction (LVEF) < institutional lower limit of normal (LLN). If the LLN is not defined at a site, the LVEF must be > 50% for the patient to be eligible.

The following groups of patients are eligible provided they have New York Heart Association class II cardiac function on baseline ECHO/nuclear study:

Patients with a history of class II heart failure who are asymptomatic on treatment
Patients with prior anthracycline exposure
Patients who have received central thoracic radiation that included the heart in the radiotherapy port NOTE: Pre-treatment LVEF determination in patients without known left ventricular dysfunction (or per Section 2.1.5.1) is NOT otherwise required
Patients with any of the following conditions are excluded:

Serious or non-healing wound, ulcer, or bone fracture
History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of treatment
Any history of cerebrovascular accident (CVA) or transient ischemic attack within 12 months prior to study entry
History of myocardial infarction, cardiac arrhythmia, stable/unstable angina, symptomatic congestive heart failure, or coronary/peripheral artery bypass graft or stenting within 12 months prior to study entry
History of pulmonary embolism within the past 12 months
Patients must not have known hypersensitivity or excess toxicity from sunitinib or compounds of similar chemical composition or biologic effect. This list includes, but is not limited to, patients with significant cardiac or hepatic toxicity from multikinase inhibitors with similar kinase inhibitory profiles (sorafenib, regorafenib, pazopanib)

Questions regarding a significant intolerance to a prior therapy should be directed to the sub-protocol principal investigator (PI)
Patients must not have had prior therapy with sunitinib
Patients must not have planned ongoing administration of STRONG and MODERATE CYP3A4 inhibitors or inducers. The reference list of cytochrome p450 (CYP) isozymes and classification of strong, moderate, and weak interactions is available through the FDA website

Strong CYP3A4 inhibitors are not permitted within 7 days before dosing and should be avoided throughout the study
Strong CYP3A4 inducers are not permitted within 12 days before dosing and should be avoided throughout the study
Patients must not have gastrointestinal stromal tumor (GIST), renal cell carcinoma, or pancreatic neuroendocrine tumor
Patients must not have a National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4 grade 3 hemorrhage within 4 weeks of starting study treatment
Patients must not have hypertension that cannot be controlled by medications (> 140/90 mmHg despite optimal medical therapy)
Patients must not have pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication
Participants may not have a major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to starting sunitinib
Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
Patients who require therapeutic doses of coumarin derivative anticoagulants such as warfarin are excluded, although doses up to 2 mg daily are permitted for prophylaxis of thrombosis NOTE: Low molecular weight heparin is permitted provided that the patient's prothrombin time (PT) international normalized ratio (INR) is < 1.5

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Lilian T Gien, ECOG-ACRIN Cancer Research Group

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Gien LT, Song Z, Poklepovic A, Collisson EA, Zwiebel JA, Gray RJ, Wang V, McShane LM, Rubinstein LV, Patton DR, Williams PM, Hamilton SR, Tricoli JV, Conley BA, Arteaga CL, Harris LN, O'Dwyer PJ, Chen AP, Flaherty KT. Phase II Study of Sunitinib in Tumors With c-KIT Mutations: Results From the NCI MATCH ECOG-ACRIN Trial (EAY131) Subprotocol V. JCO Precis Oncol. 2024 Dec;8:e2400514. doi: 10.1200/PO-24-00514. Epub 2024 Dec 12.

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